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2014 ; 522
(17
): 3861-84
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Dynamics of nascent and active zone ultrastructure as synapses enlarge during
long-term potentiation in mature hippocampus
#MMPMID25043676
Bell ME
; Bourne JN
; Chirillo MA
; Mendenhall JM
; Kuwajima M
; Harris KM
J Comp Neurol
2014[Dec]; 522
(17
): 3861-84
PMID25043676
show ga
Nascent zones and active zones are adjacent synaptic regions that share a
postsynaptic density, but nascent zones lack the presynaptic vesicles found at
active zones. Here dendritic spine synapses were reconstructed through serial
section electron microscopy (3DEM) and EM tomography to investigate nascent zone
dynamics during long-term potentiation (LTP) in mature rat hippocampus. LTP was
induced with theta-burst stimulation, and comparisons were made with control
stimulation in the same hippocampal slices at 5 minutes, 30 minutes, and 2 hours
post-induction and to perfusion-fixed hippocampus in vivo. Nascent zones were
present at the edges of ?35% of synapses in perfusion-fixed hippocampus and as
many as ?50% of synapses in some hippocampal slice conditions. By 5 minutes,
small dense-core vesicles known to transport active zone proteins moved into more
presynaptic boutons. By 30 minutes, nascent zone area decreased, without
significant change in synapse area, suggesting that presynaptic vesicles were
recruited to preexisting nascent zones. By 2 hours, both nascent and active zones
were enlarged. Immunogold labeling revealed glutamate receptors in nascent zones;
however, average distances from nascent zones to docked presynaptic vesicles
ranged from 170?±?5 nm in perfusion-fixed hippocampus to 251?±?4 nm at enlarged
synapses by 2 hours during LTP. Prior stochastic modeling suggests that decrease
in glutamate concentration reduces the probability of glutamate receptor
activation from 0.4 at the center of release to 0.1 just 200 nm away. Thus,
conversion of nascent zones to functional active zones likely requires the
recruitment of presynaptic vesicles during LTP.
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